Electron Density Map Research Articles

Understanding Large-Scale Structure in Global Ionospheric Maps With Visual and Statistical Analyses

We applied two different techniques to identify high-density structures in global maps of height-integrated electron density of the Earth’s ionosphere. We discuss benefits and limitations of these approaches to structure identification. We suggest that they are complementary and can aid our understanding of the properties of the global ionosphere. We stress out importance of a consistent definition of large-scale ionospheric structures.

A DFT study of vibrational spectra of 5-chlorouracil with molecular structure, HOMO-LUMO, MEPs/ESPs and thermodynamic properties.

The density functional theory calculation has been carried out for the analysis of 5-chlorouracil using DFT/Gaussian 09 with GAR2PED. Recorded experimental spectra for Raman and IR of 5-chlorouracil have been analyzed all fundamental vibrational modes using the outcome results of DFT at 6-311++G** of Gaussian 09 calculations and the GaussView 5.09. To help the analysis of vibrational modes, GAR2PED program has been used in the calculation of PEDs. The charge transfer properties of 5-chlorouracil have been analyzed using HOMO and LUMO level energy analysis. HOMO and LUMO energy gap study supports the charge transfer possibility in molecule. These have been made to study for reactivity and stability of heterocyclic molecules for the analysis of antiviral drugs against the new corona virus: COVID-19. Here, the smaller energy gap of 5-chlorouracil is more responsible for charge transfer interaction in the heterocyclic drug molecules and a reason of more bioactivity. The electron density mapping within molecular electrostatic potential plot and electrostatic potential plotting within iso-surface plot have been evaluated the charge distribution concept in the molecule as the nucleophilic reactions and electrophilic sites. These computations have been used to produce the molecular charges, structure and thermodynamic functions of biomolecule. This study has been made to all internal modes of chloro group substituent at pyrimidine ring of C5 atom. The splitting of frequencies has arisen in the two species for the normal distribution modes.Graphical abstract

Investigation on Quantum Computational Analysis and Toxicity Prediction of 4-Nitrophenylisocyanate

The compound 4-nitrophenylisocyanate is known for its various biological properties and class of compounds in medicinal chemistry. In this paper, we are reporting the DFT studies of 4-nitrophenylisocyanate (NPIC). To better understand molecular properties, the computational study, optimized molecular geometry, and reactive parameters were investigated and calculated by employing the method of DFT and B3LYP/6-311++G(d, p) basis set. The DFT calculations were performed to analyze the frontier molecular orbitals (HOMO-LUMO). The energy difference between HOMO - LUMO is 4.516 eV, and the MEP was traced to find the reactive sites of the compound. In addition, theoretical UV-visible spectrum and vibrational spectra (FT-IR) were obtained in the gas phase using the TD-DFT method. By using pkCSM toxicity of the compound was also predicted. The Quantum Theory of Atoms in Molecules (QTAIM) framework is used to calculate topological parameters. Different intermolecular interactions are described using terms like Reduced Density Gradient (RDG), Non-Covalent Interactions (NCI), electron density, and electron localization function and electron cloud present in the NPIC molecule.

The X-ray crystallography phase problem solved thanks to AlphaFold and RoseTTAFold models: a case-study report.

The breakthrough recently made in protein structure prediction by deep-learning programs such as AlphaFold and RoseTTAFold will certainly revolutionize biology over the coming decades. The scientific community is only starting to appreciate the various applications, benefits and limitations of these protein models. Yet, after the first thrills due to this revolution, it is important to evaluate the impact of the proposed models and their overall quality to avoid the misinterpretation or overinterpretation of these models by biologists. One ofthe first applications of these models is in solving the `phase problem' encountered in X-ray crystallography in calculating electron-density maps from diffraction data. Indeed, the most frequently used technique to derive electron-density maps is molecular replacement. As this technique relies on knowledge of the structure of a protein that shares strong structural similarity with the studied protein, the availability of high-accuracy models is then definitely critical for successful structure solution. After the collection of a 2.45 Å resolution data set, we struggled for two years in trying to solve the crystal structure of a protein involved in the nonsense-mediated mRNA decay pathway, an mRNA quality-control pathway dedicated to the elimination of eukaryotic mRNAs harboring premature stop codons. We used different methods (isomorphous replacement, anomalous diffraction and molecular replacement) to determine this structure, but all failed until we straightforwardly succeeded thanks to both AlphaFold and RoseTTAFold models. Here, we describe how these new models helped us to solve this structure and conclude that in our case the AlphaFold model largely outcompetes the other models. We also discuss the importance of search-model generation for successful molecular replacement.

Structure of the high-temperature phase of caesium nitrate - the importance of high-resolution data.

A single-crystal structure determination of the cubic phase of CsNO3 based on data collected at 439 K up to sinθmax/λ = 0.995000 Å-1, i.e. to an unprecedentedly high-θ value, is reported. The structure has been refined in Pm3m (Z = 1). Analysis of the difference electron-density maps revealed that the most appropriate model is the twelve-orientation model with the Cs, N, O1 and O2 atoms situated on the Wyckoff positions 1a, 6f, 6f and 24l, respectively, rather than the eight-orientation aragonite model with the Cs, N and O atoms situated on the Wyckoff positions 1a, 8g and 24m, respectively. Both models, however, show close similarities if the large anisotropic displacement parameters of the O atoms in the eight-orientation aragonite model are taken into account. The reason for this is shown to lie in the smeared electron density around the positions of the disordered [NO3]- anion.

DFT and experimental study on visible-light driven photocatalysis of rare-earth-doped TiO2

Visible-light driven photocatalysis of Rare-earth-doped TiO2 (RE-doped TiO2) was studied by means of density functional theory (DFT) and experiments. The band structure, density of states and difference electron density maps were calculated with DFT methods to predict the photocatalytic activity for RE-doped TiO2. The built-in electric field inhibiting the recombination of electrons and holes in Gd-doped TiO2 formed can be observed. Subsequently, the activities of these photocatalysts were evaluated, and the result indicated that Gd-doped TiO2 perform the highest photocatalytic activity, which was consistent with the theoretical prediction. In particular, the degradation efficiency of methylene blue (MB) exceeded 90% under a visible light of 405 nm wavelength within 10 min, when the content of Gd in Gd-doped TiO2 was 5 wt%. Consequently, the results indicated that enhanced photocatalytic activity was achieved at Gd modified TiO2 which mainly attributed to synergic-effect of suppressed recombination of charge-carriers, higher surface-area, optimum doping contents and extended towards visible-light absorption region.

Underdamped longitudinal soft modes in ionic crystallites-lattice and charge motions observed by ultrafast x-ray diffraction.

Soft modes in crystals are lattice vibrations with frequencies that decrease and eventually vanish as the temperature approaches a critical point, e.g., a structural change due to a phase transition. In ionic para- or ferroelectric materials, the frequency decrease is connected with a diverging electric susceptibility and, for infrared active modes, a strong increase in oscillator strength. The traditional picture describes soft modes as overdamped transverse optical phonons of a hybrid vibrational-electronic character. In this context, potassium dihydrogen phosphate (KH2PO4, KDP) has been studied for decades as a prototypical material with, however, inconclusive results regarding the soft modes in its para- and ferroelectric phase. There are conflicting assignments of soft-mode frequencies and damping parameters. We report the first observation of a longitudinal underdamped soft mode in paraelectric KDP. Upon impulsive femtosecond Raman excitation of coherent low-frequency phonons in the electronic ground state of KDP crystallites, transient powder diffraction patterns are recorded with femtosecond hard x-ray pulses. Electron density maps derived from the x-ray data reveal oscillatory charge relocations over interatomic distances, much larger than the sub-picometer nuclear displacements, a direct hallmark of soft-mode behavior. The strongly underdamped character of the soft mode manifests in charge oscillations persisting for more than 10 ps. The soft-mode frequency decreases from 0.55 THz at T = 295 K to 0.39 THz at T = 175 K. An analysis of the Raman excitation conditions in crystallites and the weak damping demonstrate a longitudinal character. Our results extend soft-mode physics well beyond the traditional picture and pave the way for an atomic-level characterization of soft modes.

Temperature and Thermal Energy of a Coronal Mass Ejection

Due to the scarcity of UV–EUV observations of coronal mass ejections (CMEs) far from the Sun (i.e., at heliocentric distances larger than 1.5 Rsun) our understanding of the thermodynamic evolution of these solar phenomena is still very limited. This work focuses on the analysis of a slow CME observed at the same time and in the same coronal locations in visible light (VL) by the MLSO Mark IV polarimeter and in the UV Lyman-α by the SOHO UVCS spectrometer. The eruption was observed at two different heliocentric distances (1.6 and 1.9 Rsun), making this work a test case for possible future multi-slit observations of solar eruptions. The analysis of combined VL and UV data allows the determination of 2D maps of the plasma electron density and also the plasma electron temperature, thus allowing the quantification of the distribution of the thermal energy density. The results show that the higher temperatures in the CME front are due to simple adiabatic compression of pre-CME plasma, while the CME core has a higher temperature with respect to the surrounding CME void and front. Despite the expected adiabatic cooling, the CME core temperatures increased between 1.6 and 1.9 Rsun from 2.4 MK up to 3.2 MK, thus indicating the presence of plasma heating processes occurring during the CME expansion. The 2D distribution of thermal energy also shows a low level of symmetry with respect to the CME propagation axis, possibly related with the CME interaction with nearby coronal structures. This work demonstrates the potential of UV and VL data combination and also of possible future multi-slit spectroscopic observations of CMEs.

From the Electron Density Gradient to the Quantitative Reactivity Indicators: Local Softness and the Fukui Function.

Important reactivity measures such as the local softness, the Fukui function, and the global hardness have been calculated directly from first principles with the use of the electron density function, beyond the finite difference approximation. Our recently derived density gradient theorem and the principle of nearsightedness of the electronic matter have been instrumental in obtaining the original, albeit approximate, result on the local softness of an atom. By integration of the local softness s(r), we obtain the global softness S and the Fukui function f(r) = s(r)/S. Local and global softness values have also been calculated analytically for the basic hydrogenic orbitals; the general relation to the atomic number S = σZ–2 has been demonstrated, with constants σ characteristic for each orbital type. Global hardness η = 1/S calculated for atoms and ions has been favorably tested against its conventional measure given by the finite difference approximation: (I – A). Calculated test results for atoms and ions in rows 1–4 of the periodic table have been presented.

Reduced zwitterionic graphene oxide sheets decorated with nickel nanoparticles as magnetically and efficient catalyst for A3‐coupling reactions under optimized green experimental conditions

A Ni‐based supported reduced zwitterionic graphene oxide N,N‐bis(2‐pyridylmethyl)ethylenediamine 1,3‐propanesultone (GO‐BPED‐PS) material was prepared for the catalysis of A3‐coupling reactions under green experimental conditions. First, the in situ generation of nickel nanoparticles (NiNPs) onto the reduced zwitterionic GO‐BPED‐PS sheets was characterized by various techniques such as Fourier infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM) analysis. Moreover, the electron density map of NiNPs onto the reduced zwitterionic GO‐based sheets was produced through the X‐ray crystallographic analysis. Then, the as‐prepared reduced GO‐BPED‐PS NiNPs (rGO‐BPED‐PS@NiNPs) material was used as a heterogeneous catalyst for the three‐component coupling reaction (A3‐coupling reaction) of benzaldehyde, morpholine, and terminal alkynes. The experimental conditions were performed in order to obtain very good green chemistry metrics. In particular, we obtained a high catalytic efficiency when using γ‐valerolactone as solvent, a reaction time of 3 h and a temperature of 100°C. In addition, it was demonstrated that the rGO‐BPED‐PS@NiNPs catalyst could be recycled for 11 times without a significant decrease in its catalytic activity.

Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques.

Water often plays a key role in protein structure, molecular recognition, and mediating protein-ligand interactions. Thus, free energy calculations must adequately sample water motions, which often proves challenging in typical MD simulation time scales. Thus, the accuracy of methods relying on MD simulations ends up limited by slow water sampling. Particularly, as a ligand is removed or modified, bulk water may not have time to fill or rearrange in the binding site. In this work, we focus on several molecular dynamics (MD) simulation-based methods attempting to help rehydrate buried water sites: BLUES, using nonequilibrium candidate Monte Carlo (NCMC); grand, using grand canonical Monte Carlo (GCMC); and normal MD. We assess the accuracy and efficiency of these methods in rehydrating target water sites. We selected a range of systems with varying numbers of waters in the binding site, as well as those where water occupancy is coupled to the identity or binding mode of the ligand. We analyzed the rehydration of buried water sites in binding pockets using both clustering of trajectories and direct analysis of electron density maps. Our results suggest both BLUES and grand enhance water sampling relative to normal MD and grand is more robust than BLUES, but also that water sampling remains a major challenge for all of the methods tested. The lessons we learned for these methods and systems are discussed.

Structural changes and photocatalytic aspects into anatase network after doping with cerium: Comprehensive study via radial distribution functions, electron density maps and molecular hardness

We present a comprehensive study of structural changes into anatase network after its doping with cerium, as well as aspects of photocatalytic processes. Additionally, structural and photocatalytic properties of Ce doped anatase can be modified by annealing temperature. The structural changes are validated by radial distribution functions and electron density maps, meanwhile the photocatalytic properties are validated by i) the molecular softness and ii) by the mineralization of 2,4-Dichlorophenoxyacetic acid (2,4-D) which is greatly improved (from 6 to 63 %) by the doping of anatase with cerium as a function of its molecular softness (from 0.34 to 0.40 eV−1). Ce doped anatase with cerium is synthesized by sol–gel method under alkaline conditions, in order to obtain ≡Ti–O–Ce–O–Ti–O–Ti≡ structures. The highest degree of mineralization is achieved by doped anatase whose molecular hardness value is the lowest (1.25 eV). Global and local properties of 2,4-D in aqueous medium are obtained by computational chemistry calculations (DFT), which suggests that the mineralization process of 2,4-D might star through the electrophilic attack from Ce doped anatase to Cl of 2,4-D in an aqueous system. Finally, the stability of TICE-III materials as photocatalysts after 4 cycles was tested.

X-ray structure of the Rhodobacter sphaeroides reaction center with an M197 Phe→His substitution clarifies the properties of the mutant complex.

The first steps of the global process of photosynthesis take place in specialized membrane pigment-protein complexes called photosynthetic reaction centers (RCs). The RC of the photosynthetic purple bacterium Rhodobacter sphaeroides, a relatively simple analog of the more complexly organized photosystem II in plants, algae and cyanobacteria, serves as a convenient model for studying pigment-protein interactions that affect photochemical processes. In bacterial RCs the bacteriochlorophyll (BChl) dimer P serves as the primary electron donor, and its redox potential is a critical factor in the efficient functioning of the RC. It has previously been shown that the replacement of Phe M197 by His strongly affects the oxidation potential of P (E m P/P+), increasing its value by 125 mV, as well as increasing the thermal stability of RC and its stability in response to external pressure. The crystal structures of F(M197)H RC at high resolution obtained using various techniques presented in this report clarify the optical and electrochemical properties of the primary electron donor and the increased resistance of the mutant complex to denaturation. The electron-density maps are consistent with the donation of a hydrogen bond from the imidazole group of His M197 to the C2-acetyl carbonyl group of BChl PB. The formation of this hydrogen bond leads to a considerable out-of-plane rotation of the acetyl carbonyl group and results in a 1.2 Å shift of the O atom of this group relative to the wild-type structure. Besides, the distance between BChl PA and PB in the area of pyrrole ring I was found to be increased by up to 0.17 Å. These structural changes are discussed in association with the spectral properties of BChl dimer P. The electron-density maps strongly suggest that the imidazole group of His M197 accepts another hydrogen bond from the nearest water molecule, which in turn appears to form two more hydrogen bonds to Asn M195 and Asp L155. As a result of the F(M197)H mutation, BChl PB finds itself connected to the extensive hydrogen-bonding network that pre-existed in wild-type RC. Dissimilarities in the two hydrogen-bonding networks near the M197 and L168 sites may account for the different changes of the E m P/P+ in F(M197)H and H(L168)F RCs. The involvement of His M197 in the hydrogen-bonding network also appears to be related to stabilization of the F(M197)H RC structure. Analysis of the experimental data presented here and of the data available in the literature points to the fact that the hydrogen-bonding networks in the vicinity of BChl dimer P may play an important role in fine-tuning the redox properties of the primary electron donor.

Deep learning-based prediction of electron density maps of proteins

Determining the structure of a protein has long been one of the most important endeavors in biology. Among the mainstream methods, X-ray diffraction contributes to more than 85% of the Protein Data Bank. There are two questions that have plagued the X-ray crystallographic community - the rationalization of protein crystallogenesis and the finding of readily usable solutions for the phase problem. In the process of X-ray diffraction, each spot in a diffraction pattern from the X-ray can be considered to have 2 main components - the intensity and the relative phase.

On the determination of ionospheric electron density profiles using multi-frequency riometry

Abstract. Radio wave absorption in the ionosphere is a function of electron density, collision frequency, radio wave polarisation, magnetic field and radio wave frequency. Several studies have used multi-frequency measurements of cosmic radio noise absorption to determine electron density profiles. Using the framework of statistical inverse problems, we investigated if an electron density altitude profile can be determined by using multi-frequency, dual-polarisation measurements. It was found that the altitude profile cannot be uniquely determined from a “complete” measurement of radio wave absorption for all frequencies and two polarisation modes. This implies that accurate electron density profile measurements cannot be ascertained using multi-frequency riometer data alone and that the reconstruction requires a strong additional a priori assumption of the electron density profile, such as a parameterised model for the ionisation source. Nevertheless, the spectral index of the absorption could be used to determine if there is a significant component of hard precipitation that ionises the lower part of the D region, but it is not possible to infer the altitude distribution uniquely with this technique alone.

Extended ensemble simulations of a SARS-CoV-2 nsp1-5'-UTR complex.

Nonstructural protein 1 (nsp1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a 180-residue protein that blocks translation of host mRNAs in SARS-CoV-2-infected cells. Although it is known that SARS-CoV-2's own RNA evades nsp1's host translation shutoff, the molecular mechanism underlying the evasion was poorly understood. We performed an extended ensemble molecular dynamics simulation to investigate the mechanism of the viral RNA evasion. Simulation results suggested that the stem loop structure of the SARS-CoV-2 RNA 5'-untranslated region (SL1) binds to both nsp1's N-terminal globular region and intrinsically disordered region. The consistency of the results was assessed by modeling nsp1-40S ribosome structure based on reported nsp1 experiments, including the X-ray crystallographic structure analysis, the cryo-EM electron density map, and cross-linking experiments. The SL1 binding region predicted from the simulation was open to the solvent, yet the ribosome could interact with SL1. Cluster analysis of the binding mode and detailed analysis of the binding poses suggest residues Arg124, Lys47, Arg43, and Asn126 may be involved in the SL1 recognition mechanism, consistent with the existing mutational analysis.

Dosimetric Effects of Air Cavities for MRI-Guided Online Adaptive Radiation Therapy (MRgART) of Prostate Bed after Radical Prostatectomy.

Purpose: To evaluate dosimetric impact of air cavities and their corresponding electron density correction for 0.35 tesla (T) Magnetic Resonance-guided Online Adaptive Radiation Therapy (MRgART) of prostate bed patients. Methods: Three 0.35 T MRgRT plans (anterior–posterior (AP) beam, AP–PA beams, and clinical intensity modulated radiation therapy (IMRT)) were generated on a prostate bed patient’s (Patient A) planning computed tomography (CT) with artificial rectal air cavities of various sizes (0–3 cm, 0.5 cm increments). Furthermore, two 0.35 T MRgART plans (‘Deformed’ and ‘Override’) were generated on a prostate bed patient’s (Patient B) daily magnetic resonance image (MRI) with artificial rectal air cavities of various sizes (0–3 cm, 0.5 cm increments) and on five prostate bed patient’s (Patient 1–5) daily MRIs (2 MRIs: Fraction A and B) with real air cavities. For each MRgART plan, daily MRI electron density map was obtained by deformable registration with simulation CT. In the ‘Deformed’ plan, a clinical IMRT plan is calculated on the daily MRI with electron density map obtained from deformable registration only. In the ‘Override’ plan, daily MRI and simulation CT air cavities are manually corrected and bulk assigned air and water density on the registered electron density map, respectively. Afterwards, the clinical IMRT plan is calculated. Results: For the MRgRT plans, AP and AP–PA plans’ rectum/rectal wall max dose increased with increasing air cavity size, where the 3 cm air cavity resulted in a 20%/17% and 13%/13% increase, relative to no air cavity, respectively. Clinical IMRT plan was robust to air cavity size, where dose change remained less than 1%. For the MRgART plans, daily MRI electron density maps, obtained from deformable registration with simulation CT, was unable to accurately produce electron densities reflecting the air cavities. However, for the artificial daily MRI air cavities, dosimetric change between ‘Deformed’ and ‘Override’ plan was small (<4%). Similarly, for the real daily MRI air cavities, clinical constraint changes between ‘Deformed’ and ‘Override’ plan was negligible and did not lead to change in clinical decision for adaptive planning except for two fractions. In these fractions, the ‘Override’ plan indicated that the bladder max dose and rectum V35.7 exceeded the constraint, while the ‘Deformed’ plan showed acceptable dose, although the absolute difference was only 0.3 Gy and 0.03 cc, respectively. Conclusion: Clinical 0.35 T IMRT prostate bed plans are dosimetrically robust to air cavities. MRgART air cavity electron density correction shows clinically insignificant change and is not warranted on low-field systems.

Quality assurance for on-table adaptive magnetic resonance guided radiation therapy: A software tool to complement secondary dose calculation and failure modes discovered in clinical routine.

Online adaption of treatment plans on a magnetic resonance (MR)‐Linac enables the daily creation of new (adapted) treatment plans using current anatomical information of the patient as seen on MR images. Plan quality assurance (QA) relies on a secondary dose calculation (SDC) that is required because a pretreatment measurement is impossible during the adaptive workflow. However, failure mode and effect analysis of the adaptive planning process shows a large number of error sources, and not all of them are covered by SDC. As the complex multidisciplinary adaption process takes place under time pressure, additional software solutions for pretreatment per‐fraction QA need to be used. It is essential to double‐check SDC input to ensure a safe treatment delivery. Here, we present an automated treatment plan check tool for adaptive radiotherapy (APART) at a 0.35 T MR‐Linac. It is designed to complement the manufacturer‐provided adaptive QA tool comprising SDC. Checks performed by APART include contour analysis, electron density map examinations, and fluence modulation complexity controls. For nine of 362 adapted fractions (2.5%), irregularities regarding missing slices in target volumes and organs at risks as well as in margin expansion of target volumes have been found. This demonstrates that mistakes occur and can be detected by additional QA measures, especially contour analysis. Therefore, it is recommended to implement further QA tools additional to what the manufacturer provides to facilitate an informed decision about the quality of the treatment plan.

Stable room temperature ferroelectricity in hydrogen-bonded supramolecular assemblies of ambipolar π-systems.

This article reports H-bonding driven supramolecular polymerization of naphthalimide (A)–thiophene (D)–naphthalimide (A) (ADnA, n = 1–4) conjugated ambipolar π-systems and its remarkable impact on room temperature ferroelectricity. Electrochemical studies confirm the ambipolar nature of these ADnA molecules with the HOMO–LUMO gap varying between 2.05 and 2.29 eV. Electron density mapping from ESP calculations reveals intra-molecular charge separation as typically observed in ambipolar systems. In the aggregated state, AD1A and AD2A exhibit bathochromically shifted absorption bands while AD3A and AD4A show typical H-aggregation with a hypsochromic shift. Polarization vs. electric field (P–E) measurements reveal stable room temperature ferroelectricity for these supramolecular assemblies, most prominent for the AD2A system, with a Curie temperature (Tc) ≈ 361 K and saturation polarization (Ps) of ∼2 μC cm−2 at a rather low coercive field of ∼2 kV cm−1. Control molecules, lacking either the ambipolar chromophore or the amide functionality, do not show any ferroelectricity, vindicating the present molecular and supramolecular design. Computational studies enable structural optimization of the stacked oligomer(s) of AD2A molecules and reveal a significant increase in the macro-dipole moment (in the range of 10–12 Debye) going from the monomer to the oligomer(s), which provides the rationale for the origin of ferroelectricity in these supramolecular polymers.

Residue Assignment in Crystallographic Protein Electron Density Maps With 3D Convolutional Networks

This work proposes a neural network architecture, called 3D FC-DenseNet, for assigning amino acid labels to X-ray crystallographic electron density maps without relying on the amino acid sequence of proteins. The 3DFC-DenseNet is able to treat the task as a 3D semantic segmentation problem, assigning amino acid labels directly to protein electron density maps. By creating dedicated data sets and models for high, medium and low resolution samples, our method matches the performance of crystallographic toolkits for primary structure assignment at high resolutions. Furthermore, it outperforms them at medium resolution and functions at low resolutions where current toolkits and human ability fails.